Population Pharmacokinetics of Paliperidone Palmitate (Once ‐Monthly Formulation) in Japanese, Korean, and Taiwanese Patients With Schizophrenia

AbstractThe paliperidone pharmacokinetics after intramuscular administration of once ‐monthly paliperidone palmitate in Japanese patients were studied in 3 phase 1 studies and in 2 phase 3 studies performed in Japan, Korea, and Taiwan. These data (Japanese, n = 509; Korean, n = 31; Taiwanese, n = 47) were used to describe the paliperidone palmitate pharmacokinetics in Japanese, to compare with non‐Japanese, and to validate the historical population pharmacokinetic (Pop‐PK) model for paliperidone palmitate, developed using data from studies in patients with schizophrenia outside Japan. The final historical Pop‐PK model, including all significant patient covariates of Ja panese studies, was used to simulate paliperidone plasma concentration–time data using nonlinear mixed effects, followed by comparison with actual data. Visual predictive checks displayed considerable overlap between predicted and actual plasma concentrations; the majority of observations were wit hin the 90% prediction interval. Japanese, Korean, and Taiwanese patients had comparable plasma concentrations. Covariate distributions demonstrated comparatively lower median body mass index in Japanese, Korean, and Taiwanese patients versus rest‐of‐world population. Prediction errors for the d ata set used for external validation were within cutoff values, confirming accuracy/precision of the model. Paliperidone pharmacokinetics were adequately predicted for Japanese studies using the historical Pop‐...
Source: Clinical Pharmacology in Drug Development - Category: Drugs & Pharmacology Authors: Tags: Original Manuscript Source Type: research